A new methodology based on gas-phase electrical mobility will be developed for measuring lipoprotein particle size distributions and will be applicable to subclass analysis. This is a technology development project and will lead to a new instrument that will resolve lipoprotein classes and subclasses. The technique is capable of quantitating lipoprotein particles, in term of mass and number, in each subclass. Currently available techniques for subclass analysis are too slow (gel electrophoresis) and too expensive (NMR spectrometry) to address the growing commercial interest in subclass analysis. If the cost of subclass analysis could be reduced, it could become a highly prescribed test because subclasses of lipoprotein particles are significantly more predictive than cholesterol tests for future coronary heart disease. Particle electrical mobility measurements reveal subclasses comparable to gradient gel electrophoresis results, but much more rapidly. Electrical mobility measuring instrumentation is much cheaper than NMR spectrometers the current obstacle confronting the widespread implementation of particle electrical mobility for subclass testing is the lack of a commercial high throughput instrument. A redesigned instrument with improved size resolution will help to make the methodology acceptable. We demonstrated the methodology using differential electrical mobility analysis. We conceptualized a next generation gas-phase particle electrical mobility spectrometer for lipoprotein analysis and propose to evaluate its design for providing high throughput lipoprotein subclass analysis and quantification.